The prognosis for most patients with high grade gliomas remains poor. Local progression remains the predominate mode of treatment failure. Resistance to radiotherapy is largely due to DNA repair, ultimately resulting recurrence and death. We are exploring the use of DNA repair inhibiting compounds as radiosensitizers for the treatment of primary brain tumors. 2-Chlorodeoxyadenosine (2CDA) is an adenosine analog which resists deamination, inhibits DNA repair, and is a potent radiosensitizer of tumor cells in vitro. 2CDA has also demonstrated single agent activity against recurrent gliomas in a phase 1 study of non-hematologic malignancies. Thus, in the present study we are conducting a phase 1 dose escalation of 2CDA given during the course of acelerated hyperfractionated radiotherapy for patients with high grade glioma or glioblastoma.